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Abstract: Dr. Sydney Finegold is one of the most heralded leaders in the discovery, classification and scientific knowledge of anaerobic bacteria. On this occasion of his 90th birthday, this paper celebrates his lifetime of accomplishments and provides a perspective on the changes and growth in our understanding of one anaerobic species, Bacteroides fragilis. Over the last nearly 40 years, clinical and research data have fostered our current view that B. fragilis are essential symbiotes as well as, in some circumstances, pathogens with the capacity to induce both acute systemic and abdominal illnesses and possibly chronic colonic diseases. [Copyright &y& Elsevier]

Abstract: Emerging data indicate that humans enjoy health through a productive collaboration with their colonizing flora, the majority of whom reside in the colon. This minireview provides a perspective on recent data and the exciting scientific challenges ahead. [Copyright &y& Elsevier]

The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host’s nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers. In this paper, we review current evidence on the role of the human microbiota in four cancer types (colorectal cancer, head and neck cancer, pancreatic cancer, and lung cancer) proposed as affected by both the oral and gut microbiota, and provide a perspective on current gaps in the knowledge of the microbiota and cancer. [ABSTRACT FROM AUTHOR]

Transition metals are required for intestinal homeostasis and provide essential nutrients for the resident microbiota. Abnormalities in metal homeostasis are common in Crohn's disease (CD), but remain poorly defined and causes appear multifactorial. There has been renewed interest in understanding these mechanisms with the discovery of an association between a coding variant in SLC39A8 (rs13107325; ZIP8 A391T) and increased CD risk. SLC39A8 encodes the protein ZIP8, a metal transporter that is induced under inflammatory stimuli; however, studies of its gut-specific functions are lacking. Here, we show that SLC39A8 mRNA is differentially expressed in active CD with a high positive correlation with markers of disease severity, including CXCL8 , TNFα , IFNγ , and calprotectin. SLC39A8 expression exhibits a negative correlation with SLC39A4 and SLC39A5 , two key zinc importers in absorptive enterocytes, and a lack of correlation with two manganese transporters, SLC39A14 and SLC11A2. Immunohistochemistry demonstrates ZIP8 expression in intestinal epithelial cells and immune cells of the lamina propria. Patients with CD exhibit variable patterns of ZIP8 subcellular localization within IECs. In ileal enteroids, SLC39A8 was induced by IFNγ and IFNγ + TNFα, but not by TNFα alone, independent of NF-κB activation. IFNγ also down-regulated SLC39A5. To explore the functional implications of disease-associated genetic variation, in over-expression experiments in HEK293A cells, ZIP8 A391T was associated with increased TNFα-induced NF-κB activation, consistent with a loss of negative regulation. Taken together, these results suggest a potential role for ZIP8 in intestinal inflammation, induced by IFNγ in the intestinal epithelial compartment, and that perturbations in negative regulation of NF-κB by ZIP8 A391T may contribute to CD pathogenesis. • SLC39A8 mRNA is increased in most severe forms of Crohn's disease. • Interferon gamma induces ZIP8 in human ileal enteroids. • Human enteroids provide a model system to study ZIP8 and metal homeostasis. • Functional experiments suggest ZIP8 A391T impairs negative regulation of NF-κB. [ABSTRACT FROM AUTHOR]